Macula densa

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

The macula densa is a dense aggregation of cells in the distal tubule of nephrons facing the glomerular tuft of capillaries. These cells sense the salt content of the distal tubular fluid and adjust glomerular perfusion and renin secretion accordingly. 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

An increase in MAP leads to an increase in RBF, PGC/ and GFR. As a result, the rate of fluid flow through the distal tubule increases, leading to an increase in reabsorption of Na+ and Cl ions by the cells of the macula densa in the distal tubule. Consequently, these cells release vasoconstrictor substances, primarily adenosine. The subsequent increase in the resistance of the nearby afferent arteriole decreases RBF to normal and, as a result, PGC and therefore GFR decrease to normal. In this way, the distal tubule regulates its own filtrate flow. 

The macula densa, which is involved in tubuloglomerular feedback, is also a factor in the regulation of renin secretion. In fact, this mechanism involving the macula densa is thought to be important in the maintenance of arterial blood pressure under conditions of decreased blood volume. For example, a decrease in blood volume leads to a decrease in RBF, GFR, and filtrate flow through the distal tubule. The resulting decrease in the delivery of NaCl to the macula densa stimulates the secretion of renin. Increased formation of angiotensin II serves to increase MAP and maintain blood flow to the tissues. 

Constitutive Inducible in neurons, macula densa of kidney testes and female reproductive system also contain constitutive COX-2... 

A correlation between the activity of G-6-PDH and extractable renin in rat kidneys has been reported, suggesting that the macula densa cells and also the juxtaglomerular apparatus are parts of a system related to the formation of renin (H6). 

There is another system involved in blood pressure regulation the renin-angiotensin-aldosterone system (Fig. 2). The arterial blood pressure in the kidney influences intrarenal baroreceptors which together with the sodium load at the macula densa lead to renin liberation, angiotensin formation and aldosterone secretion, which by influencing the sodium balance changes the blood volume and influences the arterial blood pressure. 

Renin is secreted into the bloodstream by specialised cells in a portion of the distal tubules in the kidney (known as the macula densa). The rate of secretion is stimulated by several factors, including a low Na" ion concentration in the blood and an increase in sympathetic activity (i.e. an increase in the local level of noradrenaline). 

Three generally accepted mechanisms are involved in the regulation of renin secretion (Fig. 18.2). The first depends on renal afferent arterioles that act as stretch receptors or baroreceptors. Increased intravascular pressure and increased volume in the afferent arteriole inhibits the release of renin. The second mechanism is the result of changes in the amount of filtered sodium that reaches the macula densa of the distal tubule. Plasma renin activity correlates inversely with dietary sodium intake. The third renin secretory control mechanism is neurogenic and involves the dense sympathetic... 

Increased NaCl at macula densa in distal tubule leads to decreased renin release by JG cells. 

Increased delivery of salt to the TAL leads to activation of the macula densa and a reduction in glomerular filtration rate (GFR) by tubuloglomerular (TG) feedback. The mechanism of this feedback is secretion of adenosine by macula densa cells, which locally causes afferent arteriolar vasoconstriction. This vasoconstriction reduces GFR. Tubuloglomerular feedback-mediated reduction in GFR exacerbates the reduction that was initially caused by decreased cardiac output. Recent work with adenosine receptor antagonists (eg, rolofylline) has shown that it will soon be possible to circumvent this complication of diuretic therapy in heart failure patients. Using rolofylline with a diuretic will make it possible to produce an effective diuresis in patients with heart failure without causing renal decompensation. 

The macula densa contains a different receptor mechanism that is sensitive to changes in the rate of delivery of sodium or chloride to the... 

Both the medulla and the cortex of the kidney synthesize prostaglandins, the medulla substantially more than the cortex. COX-1 is expressed mainly in cortical and medullary collecting ducts and mesangial cells, arteriolar endothelium, and epithelial cells of Bowman s capsule. COX-2 is restricted to the renal medullary interstitial cells, the macula densa, and the cortical thick ascending limb. 

The rate at which renin is secreted by the kidney is the primary determinant of activity of the renin-angiotensin system. Renin secretion is controlled by a variety of factors, including a renal vascular receptor, the macula densa, the sympathetic nervous system, and angiotensin II. 

The macula densa contains a different type of receptor, sensitive to changes in the rate of delivery of sodium or chloride to the distal tubule. Decreases in distal delivery result in stimulation of renin secretion and vice versa. Potential candidates for signal transmission between the macula densa and the juxtaglomerular cells include adenosine, prostaglandins, and nitric oxide. 

Thompson EM, Evans D J. Association of mesangial IgM with IgM deposits in the macula densa an indication of non-specific macromolecule transport rather than immune reactant Nephrol Dial Transplant 2001 16(9) 1910-3. 

Schlatter (1993) recorded membrane voltages of macula densa cells with the fast or slow whole-cell patch-clamp method. The effects of diuretics and the conductance properties of these cells were examined. 

Schlatter E (1993) Effect of various diuretics on membrane voltage of macula densa cells. Whole-cell patch-clamp experiments. Pfliigers Arch Eur J Physiol 423 74-77... 

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